异丙酚联合电休克治疗对抑郁大鼠海马谷氨酸摄取功能的影响

摘要

目的 探讨异丙酚联合电休克治疗对抑郁大鼠海马谷氨酸摄取功能的影响.方法 成年雄性SD大鼠60只,采用慢性不可预见性应激方法建立大鼠抑郁模型.待建模完成后选取抑郁评分相近的48只大鼠,通过随机数表法将其分为四组:抑郁组模型组(D组)、电休克处理组(DE组)、异丙酚处理组(DP组)和异丙酚联合电休克处理组(DPE组),每组12只.D组大鼠腹腔注射生理盐水8 mL/kg后行伪电休克处理;DE组大鼠腹腔注射生理盐水8 mL/kg后行电休克处理;DP组大鼠腹腔注射异丙酚80 mg/kg后行伪电休克处理;DPE组大鼠腹腔注射异丙酚80 mg/kg后行电休克处理.糖水偏好实验和Morris水迷宫用于行为学测试,Western blot检测海马谷氨酸转运体EAAT1/EAAT2表达,高效液相色谱检测海马谷氨酸浓度.结果 电休克及异丙酚处理前,大鼠的逃避潜伏期和空间探索时间在四组间比较差异均无统计学意义(P>0.05);电休克及异丙酚处理后,与D组相比,DE组糖水偏好百分比升高、逃避潜伏期延长、空间探索时间缩短,EAAT2表达下调,以及海马谷氨酸水平升高,差异均有统计学意义(P<0.05);与DE组相比,DPE组具有更短的逃避潜伏期和更长的空间探索时间,EAAT2表达上调及海马谷氨酸水平降低,差异均有统计学意义(P<0.05);各组大鼠海马EAAT1表达比较,差异均无统计学意义(P>0.05).结论 异丙酚预处理能够有效减轻电休克诱导的学习记忆损伤,其机制可能与上调海马EAAT2表达、改善谷氨酸摄取功能有关.%Objective To investigate the effects of propofol combined with electroconvulsive therapy (ECS) on glutamate reuptake function in hippocampal of depressive rats. Methods Sixty adult male Sprague-Dawley rats were subjected to generate animal models of depression by chronic unpredictable mild stress(CUMS).After CUMS pro-cedure was completed,forty-eight rats with similar depression scores were selected and randomly divided to four groups, using random number table: depression model group (group D), ECS treatment group (group DE), propofol treatment group(group DP),and propofol+ECS treatment group(group DPE),with 12 rats in each group.Group D were treated with pseudoelectric shock after intraperitoneal injection of normal saline for 8 mL/kg;Group DE were treated with ECS after intraperitoneal injection of normal saline for 8 mL/kg;Group DP were treated with pseudoelectric shock after intra-peritoneal injection of propofol 80 mg/kg;Group DPE were treated with ECS after intraperitoneal injection of propofol for 80 mg/kg.The sucrose preference test and Morris water maze were used to assess behavioural changes.The expres-sion levels of EAAT1 and EAAT2 were measured by western blot.High performance liquid chromatography was used to detect hippocampal glutamate concentrations.Results Before electroshock and propofol treatment,there were no sig-nificant differences in escape latency and spatial exploration time among the four groups (P>0.05).After electroshock and propofol treatment, group DE showed increased percentage of sugar water preference, prolonged escape latency, shortened spatial exploration time, decreased expression of EAAT2, and increased level of glutamate in hippocampus compared with D group, with statistically significant difference (P<0.05). Compared with group DE, group DPE had shorter escape latency,longer spatial exploration time,up-regulated EAAT2 expression and lower level of glutamate in hippocampus,with statistically significant difference(P<0.05).There were no significant differences in the expression of EAAT1 in hippocampus of all groups(P>0.05).Conclusion Propofol alleviate the learning and memory impairment in-duced by ECS,and the mechanism may be related to the up-regulation of EAAT2 expression in hippocampus and the im-provement of glutamate uptake function.